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Case Report
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J Med Cases. 2015;6(12):559-562
SAPHO Syndrome: A Chameleon in Medical Diseases
Ling Twohiga, c, Henderson Lopeza, Michelle Ngob
Abstract
SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a unique condition. Its rarity and variable presentation consummate its place within an elite group of elusory diagnosis. As a
result, the diagnosis of SAPHO syndrome is often delayed by many
years and is associated with increased medical cost, human suffering
and worsened outcome. We present an atypical presentation of the
SAPHO syndrome exhibiting an insidious onset of left hip pain with
proximal femoral diaphyseal sterile osteitis along with severe weight
loss that remained undiagnosed for over 5 years. We searched PubMed using SAPHO syndrome, unique SAPHO, SAPHO case study,
SAPHO, CMRO and diaphysis as keywords for our literature review.
The purpose of this case report is to emphasize a need for vigilance,
timely recognition and prompt treatment. We further recommend aggressive early therapy for swift symptom resolution and improved
medical outcome.
Keywords: SAPHO syndrome; SAPHO; CMRO and diaphysis
Introduction
In 1961, Windam and his team were the first to observe and
describe an association between musculoskeletal pain and skin
lesions which later became known as the SAPHO (synovitis,
acne, pustulosis, hyperostosis and osteitis) syndrome [1-3].
SAPHO is a rare condition with a prevalence of 1 in 10,000, affecting predominantly adults between ages of 30 - 50 years old,
though as young as 15 months has been observed [4]. In the
original French SAPHO cases, the gender distribution was apManuscript accepted for publication October 22, 2015
aDepartment of Internal Medicine, Arrowhead Regional Medical Center, 400
N Pepper Ave., Colton, CA 92324, USA
bDepartment of Rheumatology, Loma Linda University Medical Center, 11234
Anderson St., Loma Linda, CA 92354, USA
cCorresponding Author: Ling Twohig, Department of Internal Medicine, Arrowhead Regional Medical Center, 400 N Pepper Ave., Colton, CA 92324,
USA. Email: [email protected]
doi: http://dx.doi.org/10.14740/jmc2332w
proximately equal; however, later studies deemed female preponderance to be the majority [5, 6]. Geographically, European
reports are among the most common, and some cases from Australia and Asia have been cited; however, studies are infrequent
from North America and Latin Americas. African Americans
tend to exhibit more severe clinical presentation with heterogeneous musculoskeletal and cutaneous manifestations [7]. Due
to the heterogeneous nature in clinical manifestation, SAPHO
is often an elusive diagnosis. Its clinical and imaging findings
are often variable or may not be present at all; thus diagnosis
is often delayed by 4.5 - 9.1 years [8]. Even more concerning
is the astounding negative impact of SAPHO on the patient’s
general health and quality of life; therefore, early diagnosis and
timely treatment is of utmost importance [8].
We searched PubMed using SAPHO syndrome, unique
SAPHO, SAPHO case study, SAPHO, CMRO and diaphysis
as keywords and other relevant references were retrieved.
The purpose of our paper is to showcase an atypical presentation of SAPHO syndrome and emphasize the need for vigilance, timely recognition and prompt treatment. We present
a 64-year-old lady who arrived to our emergency department
suffering from a progressively escalated and unexplained left
thigh pain over the past 5 years, with 65 pounds of unintentional weight loss as a result of untreated SAPHO syndrome.
Case Report
A 64-year-old lady with past medical history of hypertension
presented to the emergency department complaining of severe
pain in her left thigh. Her pains started in 2009 and became
significantly worsened in the last 6 months. She also noted a
65 pound of unintentional weight loss during this time. The
patient began to experience a psoriatic, pruritic, desquamating
and tender palmoplantar pustular rash which started about 3
years ago, progressed and worsened over the past 2 months.
The rash started in her palms (Fig. 1) and in the last year, the
same rash appeared on her medial aspect of her feet (Fig. 2)
as well. Recent X-rays (Fig. 3, 4) at a prior hospital suggested
possible malignancy or infection in her left femur, thus she
was transferred for higher level of care.
On admission, the patient had decreased strength 3 out of
5 of her left lower extremity with escalating pain. Rashes on
the palms and soles were identified. Laboratory workup are
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J Med Cases. 2015;6(12):559-562
Figure 3. Skin biopsy of right palm.
Figure 1. Skin biopsy of the right foot.
Figure 2. Right foot.
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negative for white blood cell (WBC) elevation, left shift in
neutrophils, elevation in creatine kinase (CK-MB) or troponin.
XR films demonstrate periosteal reaction of proximal diaphysis. The patient was placed on ketoconazole cream and oral
steroid for the palmoplantar rashes.
On day two of hospitalization, a chest CT with contrast
negated any signs of metastatic disease or primary neoplasm.
Abdominal CT showed questionable thickened areas in sigmoid colon, left renal cyst, cystic lesions in right kidney, and
Figure 4. Right palm skin lesion.
Articles © The authors | Journal compilation © J Med Cases and Elmer Press Inc™ | www.journalmc.org
Twohig et al
J Med Cases. 2015;6(12):559-562
Figure 6. Femur under X-ray.
Figure 5. Femur under fluoroscopy.
sclerosis of the right sacral ala.
MRI of the left lower extremity demonstrated increased
T2 and decreased T1 signals of the proximal diaphysis, and
increased signals seen around the quadriceps muscle group,
which are consistent with osteomyelitis and myositis, and less
likely to be malignancy. Her whole body bone scan (technetium99m hydroxymethylene diphosphonate bone scan 99mTc HDP)
revealed abnormal activity in left proximal and mid femoral
diaphysis, sternoclavicular joints, knees, shoulders, and ankles
which favor an infection, and were unlikely to be malignant.
On day three, orthopedics and rheumatology are consulted
to biopsy the left femur and dermatology for biopsy of the skin
lesion.
Bone biopsy was taken by orthopedics with results showing reactive bony sclerosis, reactive fibrosis of the marrow
space, no inflammation, no osteomyelitis nor evidence of
tumors. Microscopically, mixtures of lamellar and reactive
woven bone were seen. In addition, myxoid areas and hemosiderin were noted in the bone marrow space while the skin
biopsy reveals sterile areas of palmoplantar pustulosis with
hypertrophy of skin (Fig. 5, 6).
During the patient’s stay, she was started on Norco 5 mg
PO Q6H, naproxen 500 mg PO BID WC, amlodipine 5 mg PO
tablet daily, gabapentin 300 mg PO capsule TID, ketorolac 15
mg IM once, ibuprofen 200 mg PO tablet Q6H, ketoconazole
cream and omeprazole 40 mg PO capsule QAMAC. Ketoconazole cream showed no significant improvement in patient’s
rashes and was discontinued on day three. Upon discharge, the
patient was given a course of naproxen for pain control and
follow-up with rheumatology clinic.
After 1 month, the patient had continued bone pain which
she was started on fosamax 75 mg PO weekly, naproxen was
switched to ibuprofen 800 mg PO TID, and continuing physical therapy. For her persistent palmoplantar skin lesions, she
was started on methotrexate 7.5 mg PO once, and increased to
15 mg PO weekly, along with folic acid of 1mg daily.
On her fourth month follow-up, her erythematous plaques
on the palms and soles were resolving, and she had no acneiform lesions. She was given clobetasol ointment for her dermatitis, and continued methotrexate and folic acid treatments.
Discussion
Diagnosis of SAPHO syndrome is challenging primarily due
to its insidious onset of symptoms and often delayed presentation or absence of any specific host manifestation at the time
of the evaluation.
SAPHO most commonly affects anterior chest wall with
associated chest pain as a manifestation of enthesopathy, synovitis, osteitis or a combination of [7]. According to Nguyen
et al, over 70% SAPHO syndrome would involve sternoclavicular manifestations, in comparison to appendicular skeleton
involvement consisting of only 5-10% of cases. In addition,
peripheral long bone involvement usually presents as osteolysis in the metaphysic adjacent to the growth plate with gradual
transform to sclerosis with hyperostosis. Invariably, all patients
will succumb to incapacitating pain frequently exacerbated by
movement or pressure [5]. In contrast, our patient did not exhibit the classic chest/back or shoulder pain. Her osteoarticular
symptoms consisted mainly of an unrelenting left thigh pain,
with abnormal bony activities in multiple appendicular skeletal locations confirmed by 99mTc HDP bone scan. Further,
typical appendicular long bone involvements primarily affect
the metaphysis adjacent to the growth plate [5]. Our patient
demonstrated diaphyseal involvement. Her bone biopsy demonstrates reactive bony sclerosis with fibrosis that conforms
to chronic bony changes as documented in prior case studies
[5]. After infectious and malignant causes were ruled out, the
suspicion of SAPHO syndrome grows stronger [9].
Another SAPHO’s diagnostic criterion is the dermatologic
manifestations that frequently accompany arthritic changes.
The skin changes often are seen as severe acne and pustulosis
palmoplantaris (PPP). Severe acne, specifically acne conglobata and acne fulminans, present in about 25% of patients [6].
PPP are detected in 50-75% of the SAPHO patients [10]. The
Articles © The authors | Journal compilation © J Med Cases and Elmer Press Inc™ | www.journalmc.org
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musculoskeletal symptoms can occur before skin involvement
in 40-68%, 30% simultaneously and late manifestation in 3260% of patients [7]. Our patient experienced the classic PPP,
however, only in the later stages of her disease. Her pustular
rash was 3 years after the onset of her leg pain, as comparison to other SAPHO cases where approximately 70% patients
will exhibit skin manifestations within 2 years from the time
of onset [4].
Because of the rarity of SAPHO syndrome, no randomized controlled trials have been conducted on the effectiveness of medical therapy. Therefore, treatments are based
on published case reports and small case series with expert
opinion. NSAIDs and analgesics are first line agents, though
therapeutic effects are limited and approximately 50% of
SAPHO patient would continue to suffer from pain and disease exacerbation [11, 12]. Alternatively, disease-modifying
anti-rheumatic drugs (DMARDs) have had some success in
some while ineffective in others. Bisphosphonates, known for
its anti-bone resorption and anti-inflammation properties, are
ideal for refractory SAPHO cases, often yielding considerable
pain relief and sustained remission. As seen in our patient, who
was initially treated and was refractory to NSAIDs therapy, her
decade of unrelenting pain improved only after the initiation of
methotrexate and fosamax [13].
Unrecognized SAPHO syndrome has a significant disease
burden according to a German nationwide patient survey [8].
On a visual analogue scale from 0 to 100, pains is logged at
45.4 ± 25.9, and mean impairment to daily activities is 62.3
± 27. Patient questionnaire further demonstrates pronounced
restriction in general health, social functioning, physical capacity, vitality, emotional and mental health [8]. Other possible complications (i.e. thrombosis, depressed mood) have been
observed in SAPHO syndrome, further supporting the merits
in early diagnosis and aggressive treatment [13, 14]. As it was
seen in our patient, after suffering 5 years of progressive pain
which may be responsible for her eventual 65 lbs weight loss,
early recognition and timely therapy could have reduced her
suffering and general health deterioration.
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Conclusion
SAPHO syndrome is difficult to diagnose due to its variable
presentations and unknown etiologies. Its rarity prohibits large
scale clinical trials to further illuminate this elusive syndrome;
hence diagnoses are often delayed by many years. However,
its high disease burden mandates physicians to remain vigilant
with a high degree of clinical suspicion. The purpose of this
case study is to raise awareness to a set of cognizant clinical
features of SAPHO syndrome as well as its atypical manifestations.
12.
Acknowledgement
14.
The authors thank Dr. Torralba for a helpful discussion at the
conception of this research.
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Articles © The authors | Journal compilation © J Med Cases and Elmer Press Inc™ | www.journalmc.org